MicroRNAs belong to a novel class of gene regulatory molecules found in plants and animals that control gene expression by binding to complimentary sequences on target mRNAs. Hundreds of miRNAs have recently been identified in worm, fly, and mammalian genomes. The function of only five miRNAs has been elucidated in animals and all five control important developmental processes. The uncharacterized miRNAs may also act as important gene regulators during development. Thirty C. elegans miRNAs are temporally regulated during development, eleven of which share homology to mammalian miRNAs. The hypothesis to be tested is that conserved temporally expressed miRNAs essential for C. elegans development will also be important during mammalian development. This proposal will 1) characterize the expression patterns of six novel conserved and temporally regulated miRNAs in C. elegans 2) determine the role of select conserved and temporally regulated miRNAs during C. elegans development and 3) investigate the function of one or two promising temporally regulated miRNA homologues in the mouse. These studies will contribute to the understanding of gene regulation and development and may lead to valuable insights on human disease.